Project Summary: The candidate is an MD/PhD with an excellent background in the molecular and cellular mechanisms of neuronal plasticity whose short-term goal is to make the transition to functional brain imaging and systems neuroscience. The candidate is also a trained clinical neurologist and his long-term career goal is to investigate the human brain's endogenous mechanisms for recovery and self-repair after stroke. The research project is driven by the realization that the dominant localizationist perspective cannot provide the answers we seek to understand brain function. Studying interhemispheric interactions is an important step toward understanding distributed brain networks. Using the novel technique of resting state functional connectivity MRI and traditional fMRI approaches will be an important step in this direction. In particular we hypothesize that resting state functional connectivity MRI can be used as an index ofthe amount of information processing taking place between the hemispheres and predicts behavioral performance. We will test this hypothesis by 1) determining resting connectivity across motor cortex in chronic stroke patients and in professional pianists compared to healthy controls and correlating connectivity with measures of hand dexterity. 2) Resting connectivity across motor cortex representing body parts of capable of different levels of unilateral movement will be studied. 3) BOLD fMRI signals generated in preparation for a unilateral hand movement will be used to study the importance of the ipsilateral BOLD signal for movement preparation and execution. Dr. Carter's career development plan will be mentored by Dr. Maurizio Corbetta, a leader in clinical neurorehabilitation and functional imaging. Consultants chosen for their expertise in functional imaging, motor control systems and computational neuroscience will provide additional guidance. Supervised research activities will be combined with didactic coursework tailored to meet Dr. Carter's needs and provide an intensive training experience. The project will be carried out at Washington University in Saint Louis, a premier site for brain imaging research. Public Health Relevance: Stroke is the leading cause of long-term disability in the United States and neurorehabilitation strategies remain woefully inadequate due to an incomplete understanding of how different parts of the brain interact with each other. The purpose of this proposal is to study how the two sides of the brain influence each other in the hope that we will develop new strategies to help people recover from brain injuries like stroke.